Study Result

Sep 12, 2018

Slides

Good day, and welcome to the Foamix Pharmaceuticals Phase 3 Data Call. Today's conference is being recorded. At this time, I'd like to turn the conference over to Michael Wood of LifeSci Advisors. Please go ahead, sir. Thank you, Derek. Good morning, everyone. Thank you for joining us. Welcome to the Foamix conference call. Leading today's call will be Dave Domzalski, Chief Executive Officer of Foamix and Doctor. Iain Stuart, Senior Vice President of R and D and Alain Hader, Chief Financial Officer of the company will also be on the call and will be available to answer questions during the Q and A session. After the market closed yesterday, Formats issued a press release summarizing the top line results from the recently completed confirmatory Phase III clinical trial of FMX101 for treatment of moderate to severe acne. If you did not yet receive the press release, it's available on the Investor Relations page of the Foamix website at foamix.com. There are also slides accompanying this call. They can be viewed by logging on to the webcast. The link is on the Investors page of the corporate website under upcoming events. And I think it's also in the press release on Page 2. This call is being recorded, and the replay will be available on the company's website. So before we begin the formal remarks, I want to remind you that some of the information in the news release and on this conference call contain forward looking statements that involve risks, uncertainties and assumptions that are difficult to predict are words that express and reflect optimism, satisfaction with current prospects or projections as well as words such as believe, intend, expect, plan, anticipate and similar variations identify forward looking statements, but their absence does not necessarily mean that a statement is not forward looking. Such forward looking statements are not a guarantee of performance, and the company's actual results could differ materially from those contained in such statements. Several factors that could cause and or contribute to such differences are described in detail in Informix's filings with the SEC. These forward looking statements speak only as of the date of the press release and today's conference call, and the company undertakes no obligation to publicly update any forward looking statements or apply new information regarding the circumstances after the date of this call. So with that, I'd like to turn the call over to Paul, our Chief CEO of Phoenix. Dave, please go ahead. Thank you, Michael, and good morning, everyone, and thank you all for joining our call today as we share the exciting results from our FMX101 4 percent minocycline foam confirmatory Phase III clinical trial known as Study FX 20 seventeen-twenty 2 or simply Study 22. This is a very exciting moment for all of us here at Foamix. By now, hopefully, you have had a chance to read the press release we issued last night. I'm very pleased to report that Study 22 successfully met both its co primary endpoints and that these results were achieved with a high magnitude of therapeutic effect and statistical significance. The safety profile of FMX101 continues to look excellent. Recall that this clinical trial was designed as a confirmatory Phase III study for FMX101 in moderate to severe acne. Following the completion of the prior Phase III studies with this drug candidate in 2017, which are studies 4 and 5, we held a Type B meeting with the FDA. We agreed with the agency at that time that statistically significant findings from a third study would constitute replication of the Study 5 results and would be sufficient for establishing an efficacy claim for FMX101. So we now believe these data, these new data we are announcing today meet this requirement, and our goal is to move forward with an NDA filing to seek approval for FMX101 in the United States. Let me begin with a review of the study design, and this is outlined on Slide 4 in the slide presentation. Study 22 is a double blind, randomized, vehicle controlled Phase III trial that enrolled 1507 patients with moderate to severe acne at 89 sites across the United States. Patients were randomized 1 to 1 to receive either FMX101 minocycline foam at a 4% concentration or vehicle foam for a 12 week period. Patients applied active drug or vehicle themselves once daily. The study was designed with 2 co primary efficacy endpoints. First, the absolute change from baseline in the number of inflammatory lesions and second, treatment success as measured by investigator global assessment or IGA score, where success was defined as an IGA score of 0 or 1, which is clear, almost clear, and at least a 2 grade improvement or decrease from baseline. In order to be included in the study, patients were required to have between 2050 inflammatory acne lesions and 25 to 100 non inflammatory lesions. Patients enrolled had either moderate or severe disease, defined as a Grade 3 or 4 on the IGA 6 point scale that we used. Because of quality issues identified at one center, 19 subjects were excluded from the intent to treat population. So the ITT, for the purposes of the efficacy analysis, comprised of 1488 patients. And the decision to exclude these patients was made well before we received the top line data. The patient demographics and baseline characteristics are presented here on next slide. For these data as well as the efficacy and safety data that I will discuss on the following slides, we are presenting it side by side with the results from Study 5 for comparison purposes. In Study 22, the baseline mean inflammatory lesion counts were 30.730.8 for the FMX101 and vehicle treatment groups, respectively. The baseline non inflammatory lesion counts were 49.749.6 for active treatment and vehicle groups, respectively, as well. In the active treatment arm, 84% of patients had an IGA score of 3, which is considered moderate acne at baseline, and 16% had a score of 4, which is severe acne. This compares with 83.5% patients in the vehicle group having a baseline score of 3 16.5 percent with a score of 4. The important thing to take away from this slide was that the patient demographics and baseline data were very similar between Studies 22 and our previous Study 5 trial. The proportion of patients with severe disease appeared slightly higher in both the active and vehicle treatment groups of Study 22 compared with the previous study. The efficacy results on the first co primary endpoint are shown here on the left hand chart of Slide 6. Patients in the FMX101 active treatment group achieved a 16.93 mean absolute reduction mean absolute reduction in the number of inflammatory lesion count from baseline to week 12. This compares with a 13.4 mean absolute reduction in the number of inflammatory lesion counts for the vehicle group. This result was highly statistically significant with a P value of less than 0 point 1. The efficacy results on this endpoint from the prior Phase III Study 5 are shown on the right. You can see the differences between active treatment and vehicle were of approximately the same magnitude across both studies. The data for the 2nd co pharma endpoint, treatment success based on IgA score, are presented on Slide 7. You can see that in Study 22, 30.8% of patients in the FMX101 treatment arm achieved treatment success compared to 19.6% of those in the vehicle arm. Once again, this result was highly statistically significant with a p value less than 0.0001. For this endpoint, there appears to be a considerable difference to what was demonstrated in Study 5. You can see in the prior Phase III study, the proportions of patients achieving treatment success were 14.7% 7.9% for the active FMX101 and vehicle arms, respectively. There are clear limitations in comparing data across our two studies being presented and will be speculative to suggest any definitive reasons for the different results. However, as we have communicated many times over the past several quarters, we have dedicated significant resources in clinical investigator training and operational management at the site level in partnership with our CRO. These efforts were led by Doctor. Ian Stewart, our Senior Vice President of Research and Development, and I want to personally recognize Ian and his entire team in the United States and Israel for their exceptional work. The charts here on Slide 8 show the percentage change in inflammatory lesion counts at weeks 3, 6, 9 and 12. This was a key secondary endpoint in both studies. At week 12, there was a 56% reduction in inflammatory lesion counts for FMX101 compared to a 43% reduction for vehicle. You can also see that in Study 22 for all time points beginning at week 3. There was a highly statistically significant percentage reduction in lesion counts for active FMX101 treatment compared with vehicle. Again, the p value at all time points was less than 0.0001. For comparison purposes, the results from Study 5 are presented on the right. The safety results from studies 22 and 5 are summarized on Slides 910. Overall, FMX101 appeared to be generally safe and well tolerated, and safety data appeared consistent with prior studies with this drug, including Study 5. The noncutaneous treatment emergent adverse events that occurred at an incidence of at least 1% of patients in Study 22 and Study 5 are listed in the table on Slide 9. The most common systemic adverse event was upper respiratory tract infection. The overall incidence of this was 6.4% in Study 22 and 6.1% in Study 5. No treatment related serious adverse events were reported in either study. In Study 22, cutaneous treatment emergent adverse events in the FMX101 treatment group were few. Most were mild, including pruritus, dermatitis, swelling, hyperpigmentation and discoloration. The actual number of events for each listed on this slide was only 1 per condition. That is it out of nearly 7 40 patients in the active group. In total, 9 subjects in Study 22 and 5 discontinued treatment due to a treatment emergent adverse event, including 5 in the FMX101 treatment group and 4 in the vehicle treatment group. Going to Slide 11 to summarize. The data from Study 22 showed strong statistically significant disease improvement of FMX101 compared with vehicle for both co primary endpoints of absolute reduction of inflammatory lesions and IgA treatment success at week 12. These data are consistent with our prior Phase III study, Study 5. FMX101 appears to be well tolerated with an excellent safety profile. In both Study 22 and 5, treatment emergent adverse events were few in type and frequency, those were mild in severity. No treatment related serious adverse events were reported. Over the next several weeks, we will receive additional data, which we will submit for presentation at various medical conferences and for publication as well as update to our investor presentations on our website. And finally, before we open the call for questions, on behalf of Foamix, I would like to thank the patients, clinical investigators and the support staffs for participating in this clinical trial. I also want to thank all my fellow colleagues at Foamix for their tremendous work and dedication. A trial such as this requires enormous effort from all those involved, and we are certainly very delighted with the outcome. With that, I'd like to turn the call back to the operator to open the line for Q and A. Operator? Thank you, sir. And we'll move to our first question from Ken Cacciatore of Cowen and Company. Please go ahead. Hey, congratulations guys on the data. I'm very happy for everyone. Dave, since the development of FMX101, the market's shifted a little bit. So wondering if you could talk about some of the dynamics in the acne market in terms of pricing and managed care. And then maybe where this would fit into the paradigm and some thoughts about maybe an analog for us to compare it to so we could get some perspective around the market opportunity? Thanks. Sure. Thanks, Ken. Of course, this market, not really unlike many markets in the pharmaceutical arena, is constantly changing. It's fluid. This market continues to be a large and sizable marketplace. Script volume, which is one that we really focus on, is around 5,000,000 scripts. Just looking at branded therapies, roughly 1,000,000 oral antibiotic branded prescriptions are written a year, about 4,000,000 branded topical prescriptions. So we continue to look at this as a large market, a multibillion dollar category. So of course, there's been changes. There have been products that have recently been genericized, but also we have new products that hopefully will be entering the market, including ours if we are successful in an ultimate NDA approval down the line. So we've done a lot of research in the space. There's significant unmet needs. We've talked about the continued opportunity of a product like ours. I think this data reflects the fact that we've shown strong efficacy. We have an excellent safety profile. We've repeatedly talked over several quarters in the last few years about how this marketplace really is yearning for safe and efficacious new products to for patients. And we believe that we hopefully will have a product that will get approved and we'll be able to address that. If you take a look at some of the leading therapies, whether it's the DAPSO molecule, the combination, adapalene Benzoyl Peroxide products, these are leading therapies in the category, large prescription volumes, large revenue generated. And we know that the oral antibiotic space is a space we believe we can take market share from that with a product like ours that we've been able to demonstrate good efficacy and an excellent safety profile with hopefully without a lot of the systemic side effects that are associated with those products. So we've always said that FMX101, if approved, has the ability to compete both within the antibiotic category as well as the topical category. And I think the results that we saw from Study 22 just further strengthens our conviction around that. So hopefully that provides some good color, Ken, for you. It does. Thanks. Congrats again. Thank you. Our next question comes from Vamil Divan of Credit Suisse. Hi, great. Thanks for taking the question. So just a couple. One, you mentioned this one center where you had issues, so you've excluded those patients. You just provide a little more detail on this and the decision to remove those even though it was done, as you said before, you saw any of the top line data? And then maybe building off of Ken's question on the commercial side, I guess, based on what you see with the data here, how do you envision sort of payer acceptance of the product? And would you envision a certain number of generics that patients don't need to go through before they can use this? Or maybe you can just kind of give us a sense of how you see the sort of treatment paradigm evolving, assuming this makes sense to the market? So I'll ask let Ian address the first question about the incentives. Ian? Ian? Thanks for the question, Donald. Yes, in relation to these 19 subjects, how these were identified during our regular clinical site monitoring activities earlier this year, so well in advance of the top line data we communicated last night. I can't go, obviously, because of the sensitivity of this issue into specifics, but it really revolves around data integrity and principal investigator oversight on the study. So we identified this early, and we took decisive action when we became aware of the issues. This was captured specifically in our statistical analytical comp prospectively and was handled way before we went anywhere near database lock and unblinding. Thanks, Ian. Amel, to further comment on reimbursement, the reimbursement landscape in our product. A couple of thoughts as we've shared repeatedly. We've done a fair amount of market research. We've not obviously determined or locked in on a potential price for our product, and we won't do that for some time, as you can appreciate. We'll continue to conduct the research, but the research has been very positive from the payer category. We've always said that we believe that this is a product that would be at a significant discount to the branded oral antibiotic therapies and in the range of the leading topical therapies. Our objective is to do what is necessary to make sure patients have access to our product if approved. That's obviously our goal. We will work with payers. We will work with patient based organizations to do whatever is necessary to ensure that our product is accessible to patients. So we continue to feel very good about that. We believe our product can address, if approved, can address unmet needs for patients and for caregivers. We believe we have a very good value proposition for the payer base. And once again, I think our results from Study 22 reinforce that position that we have. Okay. Thanks so much. Congrats on the news. Thanks. Got it. Thanks. Thank you. We'll next move to Ram Selvaraju of H. C. Wainwright. Please go ahead. Hi, there. This is Julian on for Ram. Congrats on the data. My first question is, I was just curious if you're surprised by how long the discontinuation rate was for the trial, I guess, particularly in light of trial size? No, I think it's completely consistent with our 2004 and 2005 at approximately 13% discontinuation rate. So we're satisfied with that. Okay, great. And moving on, would you characterize the safety profile of 101 as comparable across all three pivotal studies? And if not, were there any, I guess, notable differences between those studies? No. I think, broadly speaking, they were comparable. As Dave outlined during the presentation slides, the most frequent human emerging adverse event was upper respiratory tract or nasopharyngitis, common known as a common cold. So I think that was consistent across 2004, 2005 and 2022. Okay. And my last question, just looking forward, how long is it likely to take to assemble the materials necessary to file an NDA? And what might the commercial infrastructure around ONEVEER-one look like? And how long might that take to build? Sure. I'll address those questions. Regarding the timing of an NDA filing, we've completed a vast majority of the work to date. Our goal is to file an NDA by the end of this year, and we're working diligently to achieve that goal. As mentioned previously, we already had our pre NDA meeting with the FDA earlier this year. So obviously, a key component will be waiting until we get the final clinical study report from Study 22 as you can appreciate that takes a little bit of time to get all of that. We've got other components of the filing that we're working on. We've been doing this for some time. And again, our goal is to file an NDA by the end of the year. Keep everybody posted along the way. Regarding the commercial infrastructure, I'll offer a couple of thoughts. One is we'll spend the next several months conducting a lot of work around health care provider education and awareness. That will include several components, publications, congress and convention, work will be presenting our data and posters, etcetera, and then obviously continuing to work with the health care provider arena as well as with the payer base. In terms of sales force size, I know this is a question that's come up often. We've always said that sales force size would probably be somewhere in the 50 to 100 colleague range. That does not change. There's roughly around 15 1,000 active dermatologists in the United States. Of that, about onethree of them generate about 70% to 80% of the prescription volume and see the majority of the patients. So that gets you a commercial footprint in that 50 to 100 representative range, and that's fairly consistent with what you see with other organizations in the category. Could that be a little bit higher, a little bit lower? Could I think, yes, we'll determine that as we get closer to a launch. But our focus in the near term, again, will be on health care provider education and awareness. We've been doing a lot of work behind the scenes on our campaigns. And now that we have data, we'll continue to work on that with our various agency partners. We're excited about that, but our focus again will be mostly And then we'll focus on bringing their key strategic positions into the organization. We'll do that methodically. And then as we get closer to hopefully an approval and a launch. That's when we look at bringing in the sales organization. That's probably the last piece of the pie. So hopefully that provides you some good color in terms of what our next steps will be. Definitely. Thanks for that and congrats again. Thank you. Thank you. We'll next go to Patrick Dolezal of LifeSci Capital. Hi, congrats on the data and thanks for taking questions. So the first one here, I was just curious what your current manufacturing capacity is and if this will need to be scaled up as you guys move towards commercialization? Patrick, our manufacturing capacity is 1 ton. We've been at that level for some time. Our registration batches were manufactured at that scale. We have considerable stability data that's been available for some time. So we are quite confident we've been able to address the commercial needs of the marketplace at this current manufacturing scale capacity. But obviously, as we continue to move on as needed, we'll look to increase that where it warrants. But we have absolutely no concerns about our manufacturing scale capacity for a commercial launch. Great. Okay. That's helpful. And then obviously, no today's well, yesterday's data were in acne, but kind of looking forward a little bit here, what's your view on the ongoing Phase 3 program for 103 in rosacea kind of in light of the positive data in acne? Just curious if there's any potential read through here in terms of how the study is being conducted, mechanistic or otherwise? Sure, sure. As we've communicated, we've completed enrollment. We announced a few weeks back last patient enrolled in our 2 Phase III studies for FMX103, which is looking at a 1.5% concentration minocycline foam for the treatment of papillopustular rosacea. And we remain on target to having a readout from those 2 Phase III studies sometime in the earlier part of Q4. Regarding the read through, as I'm sure you can appreciate, Patrick, and everyone on the call, we're always very cautious about any kind of read through from one study to another. We're obviously, at this moment, focused on the results that we got from Study 22. And then obviously, we will announce the results from the 2 Phase III studies for 103 when they come in. What I will say in terms of where there are connections, if you will, it's the same CRO that is managing both programs. We've communicated in the past. Our CRO is Premier Research. They're out of North Carolina. They've done an excellent job for us. They're managing both programs, 101 and 103, of these Phase III studies. And I'll just underscore again, it's the same rigor and effort regarding training from our clinical operations team being executed for the 100 and 3 studies as we've done for 101. So those are the same. Beyond that, we'll just wait for the results, and we'll let you know as soon as they come in. Great. Super helpful. Looking forward to it. Thanks again. The only other point I'll add to that is that is also a sizable meaningful market. It was the logical follow on place for us in doing clinical development work. Rosacea after acne, as I shared before, acne continues to be a large market with unmet needs, multibillion dollar category with 5,000,000 branded prescriptions a year. And for the rosacea marketplace, it's about half the size, dollars 1,000,000,000 to 1,000,000,000 and $5,000,000 But unlike acne that has several players, it's got just a few products that are out there. So again, we're looking at 2 categories, both sizable, both large with significant unmet needs. And our hope is that FMX103, like FMX101, will provide a meaningful solution and alternative to address those unmet needs. Thank you. We have no further questions in the queue at this time. No, sir. Not at this time. I'd like to turn the conference back over to management for any closing or additional remarks. Well, thank you, operator. And again, thank you to everyone that's participating on this call. Appreciate you taking time out of your very busy schedules to join us. Once again, this is an exciting time for Foamix. This is a significant milestone in the history of the company. I want to again recognize everyone that's been involved in getting us here to this point. We look forward to providing you with additional updates on the data releases for 101 as they become available as well as the progress for 103 and the rest of our activities. So thank you very much. Have a great day. Look forward to speaking with all of you soon. Take care. Thank you. And ladies and gentlemen, once again, that does conclude today's conference. We thank everyone for their participation. You may now disconnect.